Recent studies from our laboratory have shown that reversible focal cerebral ischemia develops over some hours into irreversible infarction. By emergency cerebral revascularization in selected stroke cases, we have reversed neurological deficits even many hours after onset. These remarkable effects, which have now been confirmed by others, indicate that acute ischemic strokes may be reversible by appropriate therapy. Against this background, we are investigating the pathophysiology of reversible focal cerebral ischemia. An unanesthetized monkey stroke model is employed to produce atraumatic reversible middle cerebral artery occlusion in awake animals. By eliminating the confusing effects of anesthesia, this unique preparation permits serial assessment of neurological deficits, local cerebral blood flow, intracranial pressure, and eventual neuropathologic changes. The model has already demonstrated that variability in stroke derives from variability in protective collateral circulation. In preliminary studies, CBF apparently defines thresholds of ischemia for reversible paralysis and permanent infarction. further investigations are needed to characterize these important thresholds, which may be useful in prognosis. Based on these studies of reversibility, we will now evaluate acute stroke therapy, utilizing our unanesthetized monkey model. We will investigate the effectiveness of stroke treatment, including hypertension, barbiturates, and nitroglycerine.